Patients must have an acceptable MDS subtype:
Myelodysplastic syndrome (MDS), unclassifiable
Therapy-related MDS (defined as the occurrence of MDS due to prior exposure to systemic chemotherapy and/or radiation for malignancy)
Diagnosis of secondary MDS
MDS associated with 5q(del) abnormality
Myelodysplastic or myeloproliferative syndrome other than MDS.
Ongoing treatment with an anticancer agent for MDS not contemplated in this protocol.
Less than 4 weeks since any therapy for MDS
Myelodysplastic Syndrome (MDS)
AML that progressed out of myelodysplastic syndrome (MDS) is eligible if the patient did not receive treatment directed at the MDS
MDS classified as follows:
Clonal cytogenetic abnormalities consistent with pre-myelodysplastic syndrome (pre-MDS) or MDS on marrow examination (e.g. Monosomy 7).
MDS:
patients with previously treated MDS (with the exception of deletion 5q MDS) (US only)
Diagnosis of MDS according to WHO 2016 criteria
Subject has received treatment with a hypomethylating agent and/or other chemotherapeutic agent either conventional or experimental for myelodysplastic syndrome (MDS) or AML
Patients must have MDS, or MDS/MPN overlap defined by 2016 World Health Organization (WHO) criteria; both newly diagnosed or previously treated MDS or MDS/MPN patients are eligible as long as the patient has never received prior treatment with azacitidine or decitabine
A hypomethylating agent, venetoclax and/or chemo therapeutic agent for Myelodysplastic syndrome (MDS).
Diagnosis of MDS (Myelodysplastic syndromes).
Evidence of myelodysplasia (MDS); subjects with history of receiving any prior chemotherapy and/or radiotherapy for the treatment of malignant disease, history of greater than 2 months total prior cyclophosphamide for any condition (regardless of dose and route) and/or subjects presenting with abnormal peripheral blood counts require unilateral bone marrow aspiration for pathology, flow cytometry, cytogenetics, and fluorescence in situ hybridization (FISH) MDS panel (per institutional profile) to rule out MDS
secondary to MDS treated at least by hypomethylating agent or
Clonal cytogenetic abnormalities consistent with pre-myelodysplastic syndrome (pre-MDS) or MDS on marrow examination (e.g. monosomy 7)
Patients with Hypoplastic MDS defined as MDS with marrow cellularity of:
STEP 1: Within 30 days of study entry: Patients with a history of bone marrow disorders including hematological malignancies and aplastic anemia, myelodysplastic Syndrome (MDS) and myeloproliferative disorder (MPD) planning to undergo allogeneic HSCT with reduced intensity or myeloablative conditioning regimens
Patients with myelodysplastic syndrome (MDS) and myeloproliferative disorder (MPD) must have < 5% blasts in the bone marrow
DIAGNOSIS REQUIREMENT FOR PHASE I PATIENTS: Myelodysplastic syndrome (MDS) with excess blasts (> 5%) and progressive disease at any time after initiation of deoxyribonucleic acid (DNA) hypomethylator treatment during the past 2 years, OR failure to achieve complete or partial response or hematological improvement after at least six cycles of azacytidine or four cycles of decitabine administered during the past 2 years, OR intolerance to azacytidine or decitabine; MDS patients with isolated 5q- abnormalities that meet these criteria after lenalidomide therapy and DNA hypomethylator therapy are also eligible
Patients with a diagnosis of myelodysplastic syndrome/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U) that require therapy
Participant must have documented diagnosis of de novo MDS with:
Therapy-related MDS (t-MDS)
Patient with FA must have moderately severe aplastic anemia (AA) myelodysplastic syndrome (MDS) or acute leukemia with or without chromosomal abnormalities
Myelodysplastic syndrome (MDS) or myelofibrosis;
Myelodysplastic syndrome (MDS): primary or therapy related
For patients with del(5q) MDS, documented del(5q) MDS by metaphase cytogenetics or FISH analysis with up to 1 additional cytogenetic abnormality other than 1 involving chromosome 7 or chromosome 17.
Therapy related MDS.
History of other active malignancies, including myelodysplastic syndromes (MDS), within the past 3 years (exceptions described in the protocol).
Have received a hypomethylating agent for myelodysplastic syndrome (MDS).
Patient must not have a concurrent active malignancy for which they are receiving treatment (other than myelodysplastic syndromes [MDS])
Diagnosis of MDS (participants with therapy-related MDS are eligible)
Must not have received prior treatment for MDS with any hypomethylating agent
Patients with a history of myelodysplastic syndrome (MDS)
Hypoplastic MDS (cellularity < 10%).
Patients may not have undergone any prior therapy for their AML other than hydroxyurea; however, if patients had an antecedent myelodysplastic syndrome (MDS), prior treatment with a hypomethylating agent or any other therapy (with the exception of allogeneic stem cell transplant) used to treat their MDS is allowed
Patients with evidence of myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML) or abnormal cytogenetics analysis indicative of MDS on the pre-transplant bone marrow examination
Subject has received treatment with the following hypomethylating agent and/or chemo therapeutic agent for for an antecedent hematologic disorder (AHD) (Subjects may have been treated with other agents for AHD i.e., Myelodysplastic syndrome [MDS])
AML with antecedent hematological disease (e.g., myelodysplastic syndrome (MDS), myelofibrosis, polycythemia vera, etc.) and not a candidate for stem cell transplantation (SCT) in their current disease state.
AML with antecedent hematological disease (e.g., myelodysplastic syndrome (MDS), myelofibrosis, polycythemia vera, etc.) and not a candidate for SCT in their current disease state.
Known history of MDS.
Have a documented diagnosis of MDS
Secondary or hypoplastic MDS or other subtype with eligibility for treatment with immunotherapy
Known history of myelodysplastic syndrome (MDS).
Patients must have a confirmed diagnosis of non-M3 AML; antecedent myelodysplastic syndrome (MDS) is acceptable
Prior hypomethylating agent treatment for MDS
Subject has active malignant tumors other than AML or myelodysplastic syndrome (MDS).
Previous treatment with chemotherapy (cytarabine, idarubicin, daunorubicin) for a hematological disorder; Exceptions: patients with prior diagnosis of myelodysplastic syndrome (MDS) and/or treatment with hypomethylating agent (azacytidine or decitabine) are not excluded, prior hydroxyurea allowed
Previously untreated AML (except for hydroxyurea and/or corticosteroid therapy for no more than 28 days (cumulative)). Previous therapy for Myelodysplastic Syndrome (MDS) is allowed.
A pathologically confirmed diagnosis of leukemia or myelodysplastic syndrome (MDS)
The patients' leukemia or MDS blasts must express the WT1 protein detectable by immunohistopathologic analysis, or if an adequate sample is not available for testing, must have a form of leukemia (ALL, AMLs other than M5) or MDS (2 degree MDS, RAEB, RAEBT) known to overexpress WT1 in a high proportion of cases (> 60%); for patients who develop a documented relapse of leukemia or MDS following transplant, marrow aspirates should be evaluated for the proportion of blasts expressing WT1 by immunohistology or fluorescence activated cell sorting (FACS) whenever possible
Myelodysplastic syndrome (MDS): primary or therapy related; or
Received prior treatment with HMA or chemotherapy for antecedent myelodysplastic syndrome (MDS)
Previously untreated for Myelodysplastic Syndrome (MDS)
Evidence of second malignancy, abnormal cytogenetics, or morphologic evidence of myelodysplastic syndromes (MDS)
Myelodysplastic Syndrome (MDS) at any stage.
Prior treatment with decitabine for myelodysplastic syndrome (MDS) or AML
Morphologically confirmed diagnosis of MDS/CMMoL according to FAB or WHO classification, including RAEB-t and MDS/MPN
Previously untreated with hypomethylating agents for MDS/CMMoL
In blast transformation of chronic myeloid leukemia (CML). Prior myelodysplastic syndrome (MDS) is acceptable; prior treatment for MDS does not count as an AML therapy.
Diagnosis of myelodysplastic syndrome (MDS) or a hematologic malignancy.
MDS refractory to treatment with HMA therapy or with recurrence or progression of MDS following a response to an HMA
Patients with MDS with isolated del(5q)
Subject has active malignant tumors other than AML or Myelodysplastic syndrome (MDS).
Patients must have received at least one prior therapy for MDS; patients could have received transplant for MDS
Myelodysplastic syndrome (MDS)
Treatment-related MDS
Treatment-related MDS
Diagnosis of MDS or CMML
Diagnosis of myelodysplastic syndrome (MDS).
All patients who present for an initial consultation at the Dana Farber Cancer Institute (DFCI) for myelodysplastic syndrome (MDS) or a hematologic malignancy (transplantation consultation excluded)
Patients undergoing HSCT for a benign hematologic condition (myelodysplastic syndrome [MDS] is not considered a benign hematologic condition and patients with MDS are eligible for the study)
Intermediate (Int)-2 or high risk myelodysplastic syndrome (MDS)
Rapidly-progressing MDS (MYELODYSPLASTIC SYNDROMES), defined as:
A defined myelodysplastic syndrome(s) (MDS)
Histologic confirmation of leukemia or myelodysplatic syndrome (MDS) at the time of diagnosis or recurrence